James Odell, OMD, ND, L.Ac.
All content in this article is created and published online for informational purposes only. It is not intended to be a substitute for professional medical advice and should not be relied on as health or personal advice. Always seek the guidance of your doctor or other qualified health professional with any questions you may have regarding your health or a medical condition. Never disregard the advice of a medical professional, or delay in seeking it because of something you have read in this article or e-journal. Honeybee venom is toxic and may cause serious life-threatening reactions. If you choose to rely on any information provided in this article, you do so solely at your own risk.
To make a prairie it takes a clover and one bee, One clover, and a bee . . . ~ Emily Dickinson ~
Practicing the use of honeybee venom for medical conditions is part of apitherapy. Apitherapy, or therapy from honeybee products, such as honey, propolis, royal jelly, bee pollen and bee wax, has been practiced in many countries for centuries. Honeybee venom therapy (BVT), the use of live bee stings (or injectable venom), has been used for more than 3000 years in the treatment of numerous types of acute and chronic afflictions. BVT has been practiced in ancient Egypt, Greece and China — three Great Civilizations known for their highly developed medical systems. Hippocrates, a Greek physician known as the “Father of Medicine”, recognized the healing virtues of bee venom in the treatment of arthritis and other joint problems. Throughout the world many physicians are now successfully using honeybee venom therapy with success in the treatment of arthritis, multiple sclerosis, ALS, Lyme disease, psoriasis, epilepsy, asthma, and some types of cancer. The world scientific literature contains more than 1500 articles on the medicinal value of BVT.
Egyptian Hieroglyph of Honeybee
Honeybee venom is a complex mixture of various chemical compounds such as peptides, enzymes, biologically active amines and non-peptide components, some of which have strong neurological, immunological, and anti-inflammatory effects.
Honeybee venom contains more than 18 active components, of which mellitin (40-50%) is the main active peptide that exhibits anti-inflammatory, antibacterial, antiviral, and anti-carcinogenic properties.
Other components of honeybee venom:
∙ Apamin - increases the production of cortisol in the adrenal gland.
∙ Adolapin - contributes 2–5% of the peptides, acts as an anti-inflammatory and analgesic agent because it blocks cyclooxygenase-2, an enzyme responsible for inflammation and pain.
∙ Phospholipase A2 - amounts to 10–12% of peptides and is the most destructive component of apitoxin. It is an enzyme that degrades the phospholipids which compose cellular membranes. It also lowers blood pressure and inhibits blood coagulation. Phospholipase A2 activates arachidonic acid that is metabolized in the cyclooxygenase-cycle to form prostaglandins. Prostaglandins regulate the body’s inflammatory response.
∙ Hyaluronidase - contributes 1–3% of peptides, dilates the capillaries that cause the spread of inflammation.
∙ Histamine - contributes 0.5–2% and is contributes to allergic reactions.
∙ Dopamine and noradrenaline - contribute 1–2% increase in the pulse rate.
∙ Protease-inhibitors - contribute 2% and act as anti-inflammatory agents and stop bleeding.
∙Tertiapin
Unlike many other types of insect venom, honeybee venom is water-soluble, not fat-soluble. In order to be effective it is injected just under the skin into moist tissue. It’s hemorrhagic, unlike the viper snake venom, which is a coagulant. In short, honeybee venom contains anti-inflammatory properties, is mildly cytotoxic and has the contradictory effects of inhibiting the nervous system, while stimulating the heart and adrenal glands.
Mechanisms
Honeybee venom therapy is not a single mechanism, which explains why it has such a wide range of treatment applications. Several mechanisms have been proposed to describe its efficacy for the treatment of many different types of diseases. The immune system is a complicated web of communication between cells and organs, and honeybee venom stimulates key centers in the immune system by eliciting a nonspecific response. Some key mechanisms are that it stimulates the cortisone secretion, enhances antibody production, and affects cytokine production. It is also a potent inhibitor of prostaglandin formation and possesses antioxidant properties.
Conditions Treated with Honeybee Venom
Due to its bioactive substances that exhibit antioxidant, anticoagulant, and anti-inflammatory properties, honeybee venom is used to treat many disorders. In the case of chronic pain disorders such as rheumatism and arthritis, bee venom is used to control inflammation and the degeneration of connective tissue. Neurological disorders such as migraine, peripheral neuritis and chronic back pain have also been treated successfully. In the case of autoimmune disorders such as multiple sclerosis and lupus, it restores movement and mobility by enhancing the body’s natural defense mechanism. In addition, dermatological conditions such as eczema, psoriasis, and herpes may be treated effectively. Most recently, bee venom is also being investigated for treatment of cancerous tumors. 1-5Due to its antibacterial and antiviral properties, honeybee venom is also used to treat certain infectious diseases, such as Lyme disease.6, 7
Antimicrobial Effects
Honeybee venom contains a complex mixture of therapeutic compounds, including antimicrobial peptides, which allows bees to defend their hives against predators and external threats. The melittin peptide, the predominant component of bee venom (40–48%, w/w), has been substantially investigated and exhibits potent cytolytic and antimicrobial activity. Potential actions of Honeybee venom against parasites, bacteria, and viruses have been extensively examined and verified with minimal toxicity in vitro and in vivo.8, 9, 10
Inflammation and Arthritis
Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon usually leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Honeybee venom has been widely used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new options for the treatment of inflammatory diseases. Melittin is a potent anti-inflammatory agent that induces the production of cortisol in the body. Recent studies show that the anti-inflammatory properties of honeybee venom can be applied therapeutically for several types of inflammatory conditions, particularly rheumatoid and osteoarthritis.
Exact mechanisms through which honeybee venom reduces inflammation is still being investigated. The nuclear factor NF-κB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. Melittin has been shown to inhibit the activity of NF-κB. Other proposed mechanisms of reducing inflammation, such as the activation of the central and spinal opioid receptors, and α2-adrenergic activity, as well as activation of the descending serotonergic pathway have also been suggested.11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23
Nervous System Diseases
Recent clinical trials have shown that honeybee venom and its derived active components are applicable to a wide variety of neurodegenerative diseases, including multiple sclerosis and Parkinson’s disease. Such effects of honeybee venom are known to be partly mediated by modulating immune cells in the periphery and glial cells and neurons in the central nervous system.24, 25, 26
Honeybee venom has different effects on the central and peripheral nervous system and used to treat various neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson’s disease.27, 28 There are several excellent YouTube videos on the use of honeybee venom in the treatment of MS.
Changes in glutamate, the predominant excitatory neurotransmitter in the central nervous system, alters the activity of glutamate transporters in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Honeybee venom assists in reducing glutamatergic cell toxicity in neurodegenerative diseases as it protects cell death and significantly inhibits the cellular toxicity of glutamate. In one study it was shown that pretreatment with honeybee venom altered MAP kinase activation following exposure to glutamate.29
Cancer
Venoms of several animal species including honeybees have shown promising therapeutic potential against certain forms of cancer. Several studies have demonstrated that honeybee venom and/or melittin have anti-cancer effects including ovarian, prostate, liver, breast, cervical, and renal cancer cells.30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40
Honeybee venom has been widely used in the treatment of certain immune-related diseases, as well as recently in the treatment of tumors. Apoptosis, necrosis, and lysis of tumor cells have been suggested as possible mechanisms by which bee venom inhibits tumor growth. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, may be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects due to the activation of PLA2 by melittin have been suggested as a critical mechanism for the anti-cancer activity of honeybee venom. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is essential for the melittin-induced anti-cancer effects.
Administering Honeybee Venom
Traditionally, honeybee venom has been administered with live bees by stimulating them to sting in the affected area or in traditional Chinese medicine (TCM) administered on a specific acupuncture point. Current day varieties of honeybee venom products include injectable liquid venom, creams, liniments, ointments, and oral homeopathic preparations such as liquids, tablets, or capsules. Practitioners may choose the most suitable application for the condition being treated and the characteristics of the patient.
Next to the effect of a live honeybee, injectable venom solution is a standard method to administer BVT. The solution of the injectable venom is prepared from pure honeybee venom. The solution is administered under the skin to mimic the effect of a bee sting and each injection is equal to or less than the average dry venom sac content of a honeybee. Another popular way of administering BVT is with topical creams and ointments applied to the affected part of the body. For rare cases of an allergic reaction, epinephrine and Benadryl must be present before injection or administration of honeybee venom.
Acupuncture with Honeybee Venom (Api-acupuncture)
The stinging of acupuncture points with honeybees, knows as api-acupuncture, has been traditionally used in China and Japan for centuries. Bee venom acupuncture is a form of acupuncture in which bee venom is applied to acupoints on the skin by using the tips of acupuncture needles, stingers extracted from bees, or bees are held by an instrument exposing the stinger.
Collecting Honeybee Venom
Honeybee venom is synthesized in the venom glands of worker and queen bees and stored in their venom sacs. It is expressed via the sting apparatus during the stinging process. BVT is most effective when it comes from bees during the late spring to the early fall season. This is when bees have an abundant source of pollen to produce potent venom. Their venom during the winter season is less potent. The venom is normally obtained by means of electric shock stimulation. Bees come into contact with a collector frame that is covered with a wire grid and experience a mild electrical shock that causes them to release their venom. The venom is then allowed to air dry, gathered and processed. Approximately a minimum of 4000 bee stings are needed to produce 1 gram of bee venom. Traditional collection methods used up to until now typically killed the bees. However, the bee venom collected using an electro-stimulant method does not harm bees.
Reactions and Sensitivity
Honeybee venom reactions and sensitivity for most individuals typically include some redness, swelling, and itching that generally improves within a few hours. Nonetheless, an allergic individual may have a longer lasting and more severe reaction. Many individuals are allergic to the wasp, hornet, and yellow jacket stings, but few are allergic to honeybee venom. There is no cross allergy between wasp, hornet, or yellow jacket venom and honeybee venom. Because of their vegetarian nature, the chemical peptides from honeybees are different and less toxic than their carnivorous cousins. Honeybee stings are estimated to account for less than 5% of all adverse stinging insect reactions. The side effects of bee venom therapy are usually minimal as the inflammation, swelling, and itching is expected. The risk of an anaphylactic allergic reaction to honeybee venom is rare but real. It is therefore essential to have a bee sting allergy kit on hand.
Generally, a person who is not hypersensitive to bee stings can tolerate one to five stings at a time. This is followed by mild local symptoms accompanied by swelling, redness, and itchy skin. Initially, the symptoms are a little painful, but later change to a pleasant and warm sensation.
Conclusions
The use of honeybee venom for medicinal purposes can be traced back thousands of years. The therapeutic interests of honeybee venom and/or its main compounds, particularly melittin, are discussed here. The latter grants broad anti-inflammatory properties by influencing primary inflammation signaling pathways and inducing the inhibition of pro-inflammatory chemicals. Honeybee venom also exhibits neuroprotective ability in neurodegenerative diseases such as MS, Parkinson’s disease, Alzheimer’s, and ALS by significantly blocking their progression and enhancing cognitive functioning in mice models. In terms of antitumor activity, both melittin and honeybee venom have a cytotoxic effect on cancer cells and significant anti-metastatic function. The antimicrobial activity of honeybee venom also has a positive effect against a broad-spectrum of viruses, and bacteria including Borrelia b., which causes Lyme disease. The clinical acceptance of honeybee venom therapy into mainstream medicine still has a long way to go, but researchers believe that the ongoing work on this topic will eventually allow honeybee venom to be a frontline treatment for numerous diseases in upcoming years.
References:
Ram, S. K. M., Jayapal, N., Nanaiah, P., Aswal, G. S., Ramnarayan, B. K., & Taher, S. M. (2014). The therapeutic benefits of bee venom. Int. J. Curr. Microbiol. App. Sci, 3(11), 377-381.
Castro, J. I Mendez-Lnocenio, B. Omidvar, J. Omidvar, J. Santilli, H. S. Jr Nielsen, A. P. Pavot, J. R. Richert, J. A. Bellanti. 2005. "A phase I study of the safety of honeybee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis". Allergy and Asthma Proceedings. 26(6): 470- 476.
Lee, J D; Park, H J; Chae, Y; Lim, S (2005). An overview of bee venom acupuncture in the treatment of arthritis. Evidence-based complementary and alternative medicine 2 (1): 79- 84.
Liu, H.and F. Tong,( 2003). "Advances in the study of bee venom and its clinical uses". Zhong Yao Cai. Jun; 26(6):456-458.
Hwang, D. S., Kim, S. K., & Bae, H. (2015). Therapeutic effects of bee venom on immunological and neurological diseases. Toxins, 7(7), 2413-2421. Kim, H. J., & Jeon, B. S. (2014). Is acupuncture efficacious therapy in Parkinson's disease?. Journal of the neurological sciences, 341(1), 1-7.
Han, SangMi, KwangGil Lee, JooHong Yeo, HaJu Baek, and Kwankyu Park. "Antibacterial and anti-inflammatory effects of honeybee (Apis mellifera) venom against acne-inducing bacteria." Journal of Medicinal Plants Research 4, no. 6 (2010): 459-464.
Leandro, Luís F., Carlos A. Mendes, Luciana A. Casemiro, Adriana HC Vinholis, Wilson R. Cunha, Rosana de Almeida, and Carlos HG Martins. "Antimicrobial activity of apitoxin, melittin and phospholipase A2 of honey bee (Apis mellifera) venom against oral pathogens." Anais da Academia Brasileira de Ciências 87, no. 1 (2015): 147-155.
Adade, Camila M., Isabelle RS Oliveira, Joana AR Pais, and Thaïs Souto-Padrón. "Melittin peptide kills Trypanosoma cruzi parasites by inducing different cell death pathways." Toxicon 69 (2013): 227-239.
Choi, Ji Hae, A. Yeung Jang, Shunmei Lin, Sangyong Lim, Dongho Kim, Kyungho Park, Sang-Mi Han, Joo-Hong Yeo, and Ho Seong Seo. "Melittin, a honeybee venom-derived antimicrobial peptide, may target methicillin-resistant Staphylococcus aureus." Molecular medicine reports 12, no. 5 (2015): 6483-6490.
Dosler, Sibel, Elif Karaaslan, and A. Alev Gerceker. "Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria." Journal of Chemotherapy 28, no. 2 (2016): 95-103.
Chang, Yi-Han, and Marcia L. Bliven. "Anti-arthritic effect of bee venom." Agents and actions 9, no. 2 (1979): 205-211.
Eiseman, Julie L., Jurgen Von Bredow, and Alvito P. Alvares. "Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat." Biochemical pharmacology 31, no. 6 (1982): 1139-1146.
Fisher, R. B. "Bee venom and chronic inflammatory disease." The New Zealand medical journal 99, no. 808 (1986): 639.
Kwon, Young Bae, Hye Jung Lee, Ho Jae Han, Woung Chon Mar, Sung Keel Kang, Ok Byung Yoon, Alvin J. Beitz, and Jang Hern Lee. "The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats." Life sciences 71, no. 2 (2002): 191-204.
Kwon, Young-bae, Jae-dong Lee, Hye-jung Lee, Ho-jae Han, Woung-chon Mar, Sung-keel Kang, Alvin J. Beitz, and Jang-hern Lee. "Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses." Pain 90, no. 3 (2001): 271-280.
Lee, Gihyun, and Hyunsu Bae. "Anti-inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects." Molecules 21, no. 5 (2016): 616.
Lee, Jae-Dong, Hi-Joon Park, Younbyoung Chae, and Sabina Lim. "An overview of bee venom acupuncture in the treatment of arthritis." Evidence-based complementary and alternative medicine 2 (2005).
Lee, Jae-Dong, Su-Young Kim, Tae-Woo Kim, Sang-Hoon Lee, Hyung-In Yang, Doo-Ik Lee, and Yun-Ho Lee. "Anti-inflammatory effect of bee venom on type II collagen-induced arthritis." The American journal of Chinese medicine 32, no. 03 (2004): 361-367.
Lee, Ju Ah, Mi Ju Son, Jiae Choi, Ji Hee Jun, Jong-In Kim, and Myeong Soo Lee. "Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials." BMJ open 4, no. 11 (2014).
Lee, Myeong Soo, Max H. Pittler, Byung-Cheul Shin, Jae Cheol Kong, and Edzard Ernst. "Bee venom acupuncture for musculoskeletal pain: a review." The Journal of Pain 9, no. 4 (2008): 289-297.
Won, Choong-Hee, Seong-Sun Hong, Christopher MH Kim, Chong-Hee Won, Seung-Back Kang, D-Hoon Lee, Young-Do Ko, Bong-Soon Chang, and You-Young Lee. "Efficacy of apitox (bee venom) for osteoarthritis: A randomized active-controlled trial." Journal of the American Apitherapy Society 7, no. 3 (2000): 53-60.
Park, Hye Ji, Seong Ho Lee, Dong Ju Son, Ki Wan Oh, Ki Hyun Kim, Ho Sueb Song, Goon Joung Kim, Goo Taeg Oh, Do Young Yoon, and Jin Tae Hong. "Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit." Arthritis & rheumatism 50, no. 11 (2004): 3504-3515.
Zurier, R. B., H. Mitnick, D. Bloomgarden, and G. Weissmann. "Effect of bee venom on experimental arthritis." Annals of the rheumatic diseases 32, no. 5 (1973): 466.
Chung, Eun Sook, Himchan Kim, Gihyun Lee, Soojin Park, Hyunseong Kim, and Hyunsu Bae. "Neuro-protective effects of bee venom by suppression of neuroinflammatory responses in a mouse model of Parkinson’s disease: role of regulatory T cells." Brain, behavior, and immunity 26, no. 8 (2012): 1322-1330.
Hwang, Deok-Sang, Sun Kwang Kim, and Hyunsu Bae. "Therapeutic effects of bee venom on immunological and neurological diseases." Toxins 7, no. 7 (2015): 2413-2421.
Karimi, Akbar, Farhad Ahmadi, Kazem Parivar, Mohammad Nabiuni, Saied Haghighi, Sohrab Imani, and Hossein Afrouzi. "Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis." Iranian journal of pharmaceutical research: IJPR 11, no. 2 (2012): 671.
Hwang, Deok-Sang, Sun Kwang Kim, and Hyunsu Bae. "Therapeutic effects of bee venom on immunological and neurological diseases." Toxins 7, no. 7 (2015): 2413-2421.
Silva, J., Monge-Fuentes, V., Gomes, F., Lopes, K., Anjos, L. D., Campos, G., and Campos, L. (2015). Pharmacological alternatives for the treatment of neurodegenerative disorders: Wasp and bee venoms and their components as new neuroactive tools. Toxins,7(8), 3179-3209.
Lee, Sang Min, Eun Jin Yang, Sun-Mi Choi, Seon Hwy Kim, Myung Gi Baek, and Jing Hua Jiang. "Effects of bee venom on glutamate-induced toxicity in neuronal and glial cells." Evidence-based complementary and alternative medicine: eCAM 2012 (2012).
Alizadehnohi, Masoumehzaman, Mohammad Nabiuni, Zahra Nazari, Zahra Safaeinejad, and Saeed Irian. "The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp." Journal of venom research 3 (2012): 22.
Amini, Elaheh, Javad Baharara, Najmeh Nikdel, and Farzaneh Salek Abdollahi. "Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells." Asia Pacific Journal of Medical Toxicology 4, no. 2 (2015): 68-73.
Huh, Jeong-Eun, Yong-Hyeon Baek, Min-Ho Lee, Do-Young Choi, Dong-Suk Park, and Jae-Dong Lee. "Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice." Cancer letters 292, no. 1 (2010): 98-110.
Jang, Mi-Hyeon, Min-Chul Shin, Sabina Lim, Seung-Moo Han, Hi-Joon Park, Insop Shin, Ji-Suk Lee, Kyoung-Ah Kim, Ee-Hwa Kim, and Chang-Ju Kim. "Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299." Journal of pharmacological sciences 91, no. 2 (2003): 95-104.
Kim, Yong-Wan, Pankaj Kumar Chaturvedi, Sung Nam Chun, Yang Gu Lee, and Woong Shick Ahn. "Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line." Oncology reports 33, no. 4 (2015): 1675-1682.
Liu, Xing, Dawei Chen, Liping Xie, and Rongqing Zhang. "Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in‐vitro and growth of murine B16 melanomas in‐vivo." Journal of pharmacy and pharmacology 54, no. 8 (2002): 1083-1089.
Mahmoodzadeh, Amir, Hannaneh Zarrinnahad, Kamran Pooshang Bagheri, Ali Moradia, and Delavar Shahbazzadeh. "First report on the isolation of melittin from Iranian honey bee venom and evaluation of its toxicity on gastric cancer AGS cells." Journal of the Chinese Medical Association 78, no. 10 (2015): 574-583.
Oršolić, Nada, Lidija Šver, Srđan Verstovšek, Svjetlana Terzić, and Ivan Bašić. "Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom." Toxicon 41, no. 7 (2003): 861-870.
Rady, Islam, Imtiaz A. Siddiqui, Mohamad Rady, and Hasan Mukhtar. "Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy." Cancer letters 402 (2017): 16-31.
Russell, Pamela J., Dean Hewish, Teresa Carter, Katy Sterling-Levis, Kim Ow, Meghan Hattarki, Larissa Doughty et al. "Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies." Cancer Immunology, Immunotherapy 53, no. 5 (2004): 411-421.
Zarrinnahad, Hannaneh, Amir Mahmoodzadeh, Monireh Parviz Hamidi, Mehdi Mahdavi, Ali Moradi, Kamran Pooshang Bagheri, and Delavar Shahbazzadeh. "Apoptotic effect of melittin purified from Iranian honey bee venom on human cervical cancer hela cell line." International journal of peptide research and therapeutics 24, no. 4 (2018): 563-570.